Synthesis Of Amphiphilic Triblock Copolymer MPEO-b-PLC-b-PNIPAM And Their Applications In Controlled Drug Release

The self-assembled vesicles and hydrogel from stimuli-responsive polymers in aqueous solution have been intensely researched for their potential applications as drug carriers for controlled release. A series of mPEO-b-PCL-b-PNIPAM thermo sensitive triblock copolymers were synthesized,and their potential applications of self-assembled vesicles and hydrogel as drug delivery systems were investigated.(1) A series of mPEO-b-PCL-b-PNIPAM thermosensitive triblock copolymers were synthesized by anionic ring-opening polymeration(AROP),coordination-insertion ring-opening polymerization(CROP) and reversive addition-fragmentation chain transfer polymerization(RAFT).The structure and polydispersity of the amphiphilic triblock copolymer were characterized by1H-NMR and GPC in details.(2) mPEO-b-PCL-b-PNIPAM triblock copolymer vesicles were prepared according to the dialysis method. The copolymers with longer PCL blocks show lower CAC values and the advantage of the low CAC values would be experienced for nanoparticles as drug carriers. The copolymers nanoparticles exhibit a thermal response, measured by the turbidity, and the phase transition is reversible. The TEM images of the copolymers nanoparticles are spherical vesicles with a larger size at temperatures below LCST.However, when temperature increases above the LCST, the PNIPAM blocks shrank and the nanoparticles became more compact. The nanoparticles from the triblock copolymers with longer PNIPAM blocks, longer PCL blocks and greater concentration show lower LCST values. The nanoparticles from the triblock copolymers with longer PNIPAAm blocks show larger size, and the sizes of nanoparticles at40℃were smaller than at25℃.The nanoparticles shrunk greatly when increasing the temperature above the LCST, resulting in a faster release rate of indomethacin (IMC) at40℃than at25℃, indicating the acceleration functions of nanoparticle response to the thermostimulus for drug release.(3) The physical self-assembly of the triblock copolymers was used to produce the nanogels. The sol-gel phase transition diagram of copolymers aqueous solution was recorded by the tube-inverting method. Aqueous solutions of the triblock copolymers changed from the sol phase to the gel phase with increasing temperature. As the molecular weight of PCL block, PNIPAM block and the concentration of the copolymers increased, the critical gelation temperature decreased.The release of IMC from the nanogels show a faster release rate at25℃than at37℃,duing to the shrunk of PNIPAM block.The result indicates the great potential of thermosensitive nanogels as drug carriers.